Absence of pain in subjects with advanced radiographic knee osteoarthritis
ABSTRACT: Background To investigate the frequency of pain among subjects with advanced radiographic knee osteoarthritis (OA) defined as Kellgren–Lawrence (KL) grade 4 and clinical features associated with pain. Methods Subjects from the Hallym Aging Study (HAS), the Korean National Health and Nutrition Examination Survey (KNHANES), and the Osteoarthritis Initiative (OAI) were included. Participants were asked knee-specific questions regarding the presence of knee pain. Clinical characteristics associated with the presence of pain were evaluated with multivariable logistic regression analysis. Results The study population consisted of 504, 10,152 and 4796 subjects from HAS, KNHANES, and OAI, respectively. KL grade 4 OA was identified in 9.3, 7.6, and 11.5% of subjects, while pain was absent in 23.5, 31.2, and 5.9% of subjects in KL grade 4 knee OA, respectively. After multivariable analysis, female gender showed a significant association with pain in the KNHANES group, while in the OAI group, younger age did. Advanced knee OA patients without pain did not differ from non-OA subjects in most items of SF-12 in both Korean and OAI subjects. Total WOMAC score was not significantly different between non-OA and advanced knee OA subjects without pain in the OAI. Conclusions Our study showed that a considerable number of subjects with KL grade 4 OA did not report pain. In patients whose pain arises from causes other than structural damage of the joint, therapeutic decision based on knee X-ray would lead to suboptimal result. In addition, treatment options focusing solely on cartilage engineering, should be viewed with caution.
Project description:Little is known about the temporal evolution of pain severity in persons with knee osteoarthritis (OA). We sought to describe the pain trajectory over 6 years in a cohort of subjects with radiographic, symptomatic knee OA.We used data from the Osteoarthritis Initiative (OAI), a multi-center, longitudinal study of subjects with diagnosed radiographic evidence of knee OA. Pain was assessed at baseline and annually for 6 years. Our analysis cohort included subjects with symptomatic knee OA at baseline, defined as baseline Kellgren-Lawrence (KL) score ?2 with Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score >0. We used group-based trajectory modeling to identify distinct patterns of pain progression over a 6-year follow-up. Factors examined included sex, race, education, comorbidities, age, body mass index (BMI), alignment, KL grade, and depression.We used data from 1753 OAI participants with symptomatic knee OA. Mean baseline WOMAC pain score was 26.5 (0-100, 100=worst) with standard deviation (SD) 19. Group-based trajectory modeling identified five distinct pain trajectories; baseline pain scores for each ranged from 15 to 62. None of the trajectories exhibited substantial worsening. One fifth of subjects in the two trajectories with the greatest pain underwent total knee replacement (TKR) over follow-up. Higher KL grade, obesity, depression, medical comorbidities, female sex, non-white race, lower education, and younger age were associated with trajectories characterized by greater pain.We found that knee pain changes little, on average, over 6 years in most subjects. These observations suggest knee OA is characterized by persistent rather than inexorably worsening symptoms.
Project description:Objective: we aimed to identify circulating microRNAs associated with fast-progressing knee osteoarthritis (OA) as compared to slow-progressing knee OA and non-progressing knee OA using sujects from the Osteoarthritis Initiative (OAI) cohort. MicroRNA libraries were prepared from plasma using the QIAseq miRNA Library Kit (QIAGEN) and sequenced on the Illumina NextSeq550 using a single-end 75-base read protocol to an average depth of 11.6 ± 2.6 SD million reads per sample. Overall design: MicroRNA-sequencing was performed on plasma collected at baseline and 4-year follow-up from N=20 fast-progressors (Kellgren-Lawrence [KL] grade 0/1 at baseline to KL 3/4 by 4-year follow-up), N=35 slow-progressors (KL 0/1 at baseline and 4-year follow-up to KL 2/3/4 by 8-year follow-up), and N=51 non-progressors (KL 0/1 at baseline through to 8-year follow-up).
Project description:BACKGROUND:Osteoarthritis (OA), a multifactorial disease causing joint degeneration, often leads to severe disability. The rising rates of disability highlight the need for implementing preventative measures at early stages of the disease, which would especially benefit subjects at high risk for OA development. PURPOSE:To develop a risk prediction tool for moderate-severe OA (TOARP) over 8 years based on subject characteristics, knee radiographs, and MRI data at baseline using data from the Osteoarthritis Initiative (OAI). STUDY TYPE:Retrospective. SUBJECTS:641 subjects with no/mild radiographic OA (Kellgren-Lawrence [KL] 0-2) and no clinically significant symptoms (Western Ontario and McMaster Universities Arthritis Index [WOMAC] 0-1) were selected from the OAI. FIELD STRENGTH/SEQUENCE:MR images were obtained using 3.0T. ASSESSMENT:Compartment-specific cartilage and meniscus morphology and cartilage T2 were assessed. Baseline subject demographics, risk factors, KL score, cartilage WORMS score, presence of meniscus tear, and cartilage T2 were used to predict the development of moderate/severe OA (KL = 3-4 or WOMAC pain ?5 or total knee replacement [TKR]) over 8 years. STATISTICAL TESTS:Best subsets variable selection followed by cross-validation were used to assess which combinations of variables best predict moderate/severe OA. RESULTS:Model 1 included KL score, previous knee injury in the last 12 months, age, gender, and BMI. Model 2 included all variables in Model 1 plus presence of cartilage defects in the lateral femur and patella, and presence of a meniscal tear. Model 3 included all variables in Models 1 and 2, plus cartilage T2 in the medial tibia and medial femur. Compared to Model 1 (cross-validated AUC = 0.67), Model 3 performed significantly better (AUC = 0.72, P = 0.04), while Model 2 showed a statistical trend (AUC = 0.71, P = 0.08). DATA CONCLUSION:We established a risk calculator for the development of moderate/severe knee OA over 8 years that includes radiographic and MRI data. The inclusion of MRI-based morphological abnormalities and cartilage T2 significantly improved model performance. LEVEL OF EVIDENCE:2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:1517-1526.
Project description:<h4>Background</h4>Knee osteoarthritis (OA) is the most common joint disease of adults worldwide. Since the treatments for advanced radiographic knee OA are limited, clinicians face a significant challenge of identifying patients who are at high risk of OA in a timely and appropriate way. Therefore, we developed a simple self-assessment scoring system and an improved artificial neural network (ANN) model for knee OA.<h4>Methods</h4>The Fifth Korea National Health and Nutrition Examination Surveys (KNHANES V-1) data were used to develop a scoring system and ANN for radiographic knee OA. A logistic regression analysis was used to determine the predictors of the scoring system. The ANN was constructed using 1777 participants and validated internally on 888 participants in the KNHANES V-1. The predictors of the scoring system were selected as the inputs of the ANN. External validation was performed using 4731 participants in the Osteoarthritis Initiative (OAI). Area under the curve (AUC) of the receiver operating characteristic was calculated to compare the prediction models.<h4>Results</h4>The scoring system and ANN were built using the independent predictors including sex, age, body mass index, educational status, hypertension, moderate physical activity, and knee pain. In the internal validation, both scoring system and ANN predicted radiographic knee OA (AUC 0.73 versus 0.81, p<0.001) and symptomatic knee OA (AUC 0.88 versus 0.94, p<0.001) with good discriminative ability. In the external validation, both scoring system and ANN showed lower discriminative ability in predicting radiographic knee OA (AUC 0.62 versus 0.67, p<0.001) and symptomatic knee OA (AUC 0.70 versus 0.76, p<0.001).<h4>Conclusions</h4>The self-assessment scoring system may be useful for identifying the adults at high risk for knee OA. The performance of the scoring system is improved significantly by the ANN. We provided an ANN calculator to simply predict the knee OA risk.
Project description:OBJECTIVES:Knee osteoarthritis (OA) onset and progression has been defined with transitions in Kellgren-Lawrence (KL) grade or Osteoarthritis Research Society International (OARSI) Joint Space Narrowing (JSN) grade. We quantitatively describe one-year transitions in KL grade and JSN, using fixed joint space width (fJSW), among knees with or at risk of OA. METHODS:Radiographic assessments from the Osteoarthritis Initiative (OAI) were used to identify transitions in KLG and JSN grade between consecutive annual visits. The fJSW was measured in the medial and lateral compartments. The distribution of change in fJSW for KLG and JSN transitions were described, and mean change in fJSW was estimated using mixed models. RESULTS:KL grade and JSN scores were available for about 20,000 annual transitions from 6047 knees contributed by 3389 participants. Knees that remained stable in KL or OARSI-JSN over 1 year had mean medial fJSW loss between -0.06 and -0.19 mm/year. Transition from KL grade 0 to 1, 0 to 2, and KL 1 to 2 were similar with respect to mean medial fJSW loss (0.18-0.28 mm). Greatest annual changes in medial fJSW corresponded to KL 0 to 3 (1.62 mm), KL 2 to 4 (1.23 mm) and JSN 0 to 2 (1.85 mm). CONCLUSIONS:Anchoring quantitatively measured loss of joint space width to transitions in KL grade and JSN provides reference values based on traditional definitions of knee OA onset and progression.
Project description:BACKGROUND:To reduce the social burden of knee osteoarthritis (OA) by addressing it in the early stages in the population at greatest risk, the epidemiology of knee OA needs to be understood and associated demographic factors need to be identified. OBJECTIVES:We evaluated the weighted prevalence of and demographic factors associated with radiographic knee OA in Korean adults. METHODS:We analyzed data from 12,287 individuals aged ? 50 years who had radiographs of the knee taken in the 2010-2013 Korea National Health and Nutrition Examination Survey (KNHANES). Radiographic knee OA was defined based on the Kellgren-Lawrence grade, as follows: 0: No abnormal finding 1: Mild degenerative changes, minute osteophytes 2: Mild knee OA, definite osteophytes 3: Moderate knee OA, moderate joint-space narrowing and definite osteophytes 4: Severe knee OA, severe joint-space narrowing with subchondral sclerosis. RESULTS:We found that the prevalence of radiographic knee OA in the Korean adult population was 35.1%. Logistic regression analyses were performed to identify factors associated independently with radiographic knee OA, with age, sex, area of residence, education level, household income, and obesity serving as covariates. Women were at greater risk than men of having knee OA (OR 2.12, 95% CI 1.90-2.37, p < 0.001). Compared with subjects aged 50-59 years, adults aged ? 80 years were at 8.87-fold (95% CI 7.12-11.06, p < 0.001) greater risk of having knee OA. Residence in a rural area was associated with a greater risk of having radiographic knee OA than was residence in an urban area (OR 1.26, 95% CI 1.08-1.48, p = 0.004), regardless of knee OA severity (Kellgren-Lawrence grades ?2, ?3, and 4). Elementary school graduates had 1.71-fold (p < 0.001) greater risks of having knee OA than did college graduates. Household incomes ?24th percentile were associated with a greater risk of having knee OA compared with those ?75th percentile (OR 1.28, 95% CI 1.08-1.52, p = 0.004). Obesity was associated with an approximately two-fold greater risk of knee OA, regardless of knee OA severity (Kellgren-Lawrence grades ?2, ?3, and 4). CONCLUSIONS:Using data from the 2010-2013 KNHANES and defining knee OA as Kellgren-Lawrence grade ? 2, we found that the prevalence of radiographic knee OA was 35.1% (24.4% in men, 44.3% in women) in a representative sample of Korean adults aged ? 50 years, with the highest prevalence (78.7%) observed in women aged ? 80 years. Low socioeconomic status and traditional factors, including age, female sex, and obesity, were associated with the risk of knee OA.
Project description:OBJECTIVE:To investigate whether foot and/or ankle symptoms increase the risk of developing (1) knee symptoms and (2) symptomatic radiographic knee osteoarthritis (OA). DESIGN:1020 Osteoarthritis Initiative (OAI) participants who were at-risk of knee OA, but were without knee symptoms or radiographic knee OA, were investigated. Participants indicated the presence and laterality of foot/ankle symptoms at baseline. The main outcome was development of knee symptoms (pain, aching or stiffness in and around the knee on most days of the month for at least 1 month in the past year). A secondary outcome was development of symptomatic radiographic knee OA (symptoms plus Kellgren and Lawrence [KL] grade ?2), over the subsequent 4 years. Associations between foot/ankle symptoms and study outcomes were assessed by logistic regression models. RESULTS:Foot/ankle symptoms in either or both feet significantly increased the odds of developing knee symptoms (adjusted odds ratio (OR) 1.55, 95% confidence interval (CI) 1.10 to 2.19), and developing symptomatic radiographic knee OA (adjusted OR 3.28, 95% CI 1.69 to 6.37). Based on laterality, contralateral foot/ankle symptoms were associated with developing both knee symptoms (adjusted OR 1.68, 95% CI 1.05 to 2.68) and symptomatic radiographic knee OA (adjusted OR 3.08, 95% CI 1.06 to 8.98), whilst bilateral foot/ankle symptoms were associated with developing symptomatic radiographic knee OA (adjusted OR 4.02, 95% CI 1.76 to 9.17). CONCLUSION:In individuals at-risk of knee OA, the presence of contralateral foot/ankle symptoms in particular increases risk of developing both knee symptoms and symptomatic radiographic knee OA.
Project description:To study the interrelationship between patella cartilage T2 relaxation time, other knee abnormalities, and physical activity levels in asymptomatic subjects from the Osteoarthritis Initiative (OAI) incidence cohort.The study had institutional review board approval and was HIPAA compliant. One hundred twenty subjects from the OAI without knee pain (age, 45-55 years) and with risk factors for knee osteoarthritis (OA) were studied by using knee radiographs, 3.0-T knee magnetic resonance (MR) images (including intermediate-weighted fast spin-echo and T2 mapping sequences), and the Physical Activity Scale for the Elderly. MR images of the right knee were assessed by two musculoskeletal radiologists for the presence and grade of abnormalities. Segmentation of the patella cartilage was performed, and T2 maps were generated. Statistical significance was determined by using analysis of variance, chi(2) analysis, correlation coefficient tests, the Cohen kappa, and a multiple linear regression model.Cartilage lesions were found in 95 (79.0%) of 120 knees, and meniscal lesions were found in 54 (45%) of 120 knees. A significant correlation between patella cartilage T2 values and the severity and grade of cartilage (P = .0025) and meniscus (P = .0067) lesions was demonstrated. Subjects with high activity levels had significantly higher prevalence and grade of abnormalities and higher T2 values (48.7 msec +/-4.35 vs 45.8 msec +/-3.93; P < .001) than did subjects with low activity levels.Middle-aged asymptomatic individuals with risk factors for knee OA had a high prevalence of cartilage and meniscus knee lesions. Physically active individuals had more knee abnormalities and higher patellar T2 values. Additional studies will be needed to determine causality.
Project description:Diabetes has been proposed as a factor involved in the pathogenesis of osteoarthritis (OA). Currently, there is a lack of research evaluating the prospective impact of diabetes on OA structural outcomes. In this study, we assessed the effects of medication-treated diabetes on incidence and progression of knee OA. We analysed longitudinal data from the multi-center, longitudinal, prospective observational Osteoarthritis Initiative (OAI) study. The main outcomes were radiographic OA incidence (development of Kellgren-Lawrence grade 2 with joint space narrowing, JSN) and progression (increase in semiquantitative JSN or a new knee replacement). For the study of incidence, we selected participants with KL <2 or /KL?=?2 without JSN at baseline (incidence sample). To evaluate progression, we selected participants with baseline JSN <3 (progression sample). We used generalized estimating equations (GEE) logistic regression with adjustment for potential confounders to evaluate the effects of medication-treated diabetes on knee OA incidence and progression. We studied 3725 knees (3498 non-diabetic and 228 diabetic) in the incidence sample and 3594 knees (3335 non-diabetic and 259 diabetic) in the progression sample. Medication-treated diabetes did not have an effect on knee OA incidence (odds ratio, OR 0.53, 95% confidence interval, CI 0.23-1.5). There was an independent association between medication-treated diabetes and reduced progression of knee OA [OR 0.66, 95% CI (0.44-0.98)]. Medication-treated diabetes has no effect on knee OA incidence but reduces knee OA progression. The role of diabetes and anti-diabetic drugs in knee OA progression needs further exploration.